HIV linked to lower rifampin and ethambutol AUCs in TB cohort

HIV infection independently predicted lower rifampin and ethambutol exposure in a cohort of 142 people beginning first-line therapy for drug-sensitive pulmonary tuberculosis.

South African researchers measured 8-hour area under the concentration-time curve (AUC) for rifampin, isoniazid, pyrazinamide, and ethambutol after 2 months of daily in-hospital treatment. They used multiple linear regression to sort out variables associated with variation in AUCs.

HIV infection correlated with a 39% lower rifampin AUC and a 27% lower ethambutol AUC. Women had higher rifampin and isoniazid AUCs than men but lower ethambutol concentrations. Older patients had higher levels of isoniazid and ethambutol. Patients with a history of anti-TB therapy had lower ethambutol concentrations. And dose per kilogram of body weight correlated with AUCs of all four drugs.

The authors caution further studies are required to assess the implications of variations in antituberculosis drug concentrations for efficacy and safety before decisions are made to change the dosing strategy in patients at risk.

Helen McIlleron, Peter Wash, André Burger, Jennifer Norman, Peter I. Folb, Pete Smith. Determinants of rifampin, isoniazid, pyrazinamide, and ethambutol pharmacokinetics in a cohort of tuberculosis patients. Antimicrob Agents Chemther 2006;50:1170-1177.